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We previously reported that a combined myo -inositol, probiotics, and enriched micronutrient supplement (intervention) taken preconception and in pregnancy reduced postpartum blood loss (PBL) and major postpartum hemorrhage compared with a standard micronutrient supplement (control), as secondary outcomes of the NiPPeR trial. This study aimed to identify the intervention components that may contribute to this effect. Associations of plasma concentrations of myo -inositol and vitamins B2, B6, B12, and D at preconception (before and after supplementation), early (~7-weeks), and late pregnancy (~28-weeks) with PBL were assessed by multiple linear regression, adjusting for site, ethnicity, preconception BMI, parity, and previous cesarean section. Amongst 583 women, a higher concentration of myo -inositol in early pregnancy was associated with a PBL reduction [β adj -1.26 (95%CI -2.23, -0.29) mL per µmol/L myo -inositol increase, p = 0.011]. Applying this co-efficient to the increase in mean 7-week- myo -inositol concentration of 23.4 µmol/L with the intervention equated to a PBL reduction of 29.5 mL (~8.4% of mean PBL of 350 mL among controls), accounting for 84.3% of the previously reported intervention effect of 35 mL. None of the examined vitamins were associated with PBL. Therefore, myo -inositol may be a key intervention component mediating the PBL reduction. Further work is required to determine the mechanisms involved., Competing Interests: S.-Y.C., W.S.C., and K.M.G. are part of an academic consortium that report grants from Société Des Produits Nestlé S.A. during the conduct of the study and are co-inventors on patent filings by Nestlé S.A. relating to the NiPPeR intervention or its components. S.-Y.C. has received reimbursement and honoraria into her research funds from Nestlé Nutrition Institute and EGOI (Experts Group on Inositols) for speaking at conferences. K.M.G. has received reimbursement for speaking at conferences sponsored by companies selling nutritional products. L.L., J.M.R.-N., J.-P.G., and I.S.-Z. are employees of Société Des Produits Nestlé S.A. All other authors declare no competing interests.

Background: While the bioavailability of cocoa polyphenols, particularly of the monomer (-)-epicatechin, has been investigated after a single-dose intake, the effect of sustained cocoa consumption on the metabolic profile of the structurally related (-)-epicatechin metabolites (SREMs) has not been investigated., Methods: A randomized, controlled crossover clinical trial in healthy young adults (18-40 year) was conducted to evaluate SREMs after consumption of a single-dose and after daily consumption of 1.3 g of polyphenol-rich cocoa powder for 28 days. The circulating SREMs were measured by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS)., Results: Twenty subjects (eleven males and nine females) were enrolled. The SREMs concentrations increased to 1741 ± 337 nM after a single-dose and to 1445 ± 270 nM after sustained supplementation. Sulfate conjugates showed higher levels in females ( p < 0.05). The epicatechin-3'-glucuronide (E3'G) and epicatechin-3'-sulfate (E3'S) were the most abundant metabolites in all subjects. A high intra-individual correlation (r = 0.72, p < 0.001) between SREMs concentrations after single-dose and sustained supplementation was observed. The antioxidant capacity of plasma did not change in response to the intervention and was not correlated with any of the SREMs., Conclusion: The individual SREMs profile and concentrations after a 28-day supplementation are comparable to those after a single dose.

Glucose intolerance during pregnancy - a major driver of gestational diabetes mellitus (GDM) - has significant short- and long-term health consequences for both the mother and child. As GDM prevalence continues to escalate, there is growing need for preventative strategies. There is limited but suggestive evidence that myo-inositol (MI) and probiotics (PB) could improve glucose tolerance during pregnancy. The present study tested the hypothesis that MI and/or PB supplementation would reduce the risk of glucose intolerance during pregnancy. Female C57BL/6 mice were randomised to receive either no treatment, MI, PB (Lactobacillus rhamnosus and Bifidobacterium lactis) or both (MIPB) for 5 weeks. They were then provided with a high-fat diet for 1 week before mating commenced and throughout mating/gestation, while remaining on their respective treatments. An oral glucose tolerance test occurred at gestational day (GD) 16·5 and tissue collection at GD 18·5. Neither MI nor PB, separately or combined, improved glucose tolerance. However, MI and PB both independently increased adipose tissue expression of Ir, Irs1, Akt2 and Pck1, and PB also increased Pparγ. MI was associated with reduced gestational weight gain, whilst PB was associated with increased maternal fasting glucose, total cholesterol and pancreas weight. These results suggest that MI and PB may improve insulin intracellular signalling in adipose tissue but this did not translate to meaningful differences in glucose tolerance. The absence of fasting hyperglycaemia or insulin resistance suggests this is a very mild model of GDM, which may have affected our ability to assess the impact of these nutrients.

Vitamin B12 (B-12) deficiency is still relatively common in low-, medium-, and high-income countries, mainly because of dietary inadequacy and, to a lesser extent, malabsorption. This narrative review is based on a systematic search of evidence on methods to assess B-12 bioavailability and technologies to enhance its absorption. A total of 2523 scientific articles identified in PubMed and 1572 patents identified in Orbit Intelligence were prescreened. Among the reviewed methods, Schilling's test and/or its food-based version (using cobalamin-labeled egg yolk) were used for decades but have been discontinued, largely because they required radioactive cobalt. The qualitative CobaSorb test, based on changes in circulating holo-transcobalamin before and after B-12 administration, and the 14C-labeled B-12 test for quantitative measurement of absorption of a low-dose radioactive tracer are currently the best available methods. Various forms of B-12 co-formulated with chemical enhancers (ie, salcaprozate sodium, 8-amino caprylate) or supplied via biotechnological methods (ie, microbiological techniques, plant cells expressing cobalamin binding proteins), encapsulation techniques (ie, emulsions, use of chitosan particles), and alternative routes of administration (ie, intranasal, transdermal administration) were identified as potential technologies to enhance B-12 absorption in humans. However, in most cases the evidence of absorption enhancement is limited.

Gestational diabetes mellitus (GDM) is a growing concern, affecting an increasing number of pregnant women worldwide. By predisposing both the affected mothers and children to future disease, GDM contributes to an intergenerational cycle of obesity and diabetes. In order to stop this cycle, safe and effective treatments for GDM are required. This study sought to determine the treatment effects of dietary supplementation with myo-inositol (MI) and vitamins B2, B6, B12, and D in a mouse model of GDM (pregnant db/+ dams). In addition, the individual effects of vitamin B2 were examined. Suboptimal B2 increased body weight and fat deposition, decreased GLUT4 adipose tissue expression, and increased expression of inflammatory markers. MI supplementation reduced weight and fat deposition, and reduced expression of inflammatory markers in adipose tissue of mice on suboptimal B2. MI also significantly reduced the hyperleptinemia observed in db/+ mice, when combined with supplemented B2. MI was generally associated with adipose tissue markers of improved insulin sensitivity and glucose uptake, while the combination of vitamins B2, B6, B12, and D was associated with a reduction in adipose inflammatory marker expression. These results suggest that supplementation with MI and vitamin B2 could be beneficial for the treatment/prevention of GDM.